Long-term insulin independence in type 1 diabetes mellitus using a simplified autologous stem cell transplant

Abstract

Context: Efforts to find a cure for type 1 diabetes have focused on the removal of the autoimmune pathophysiologic substrate, with the use of immunosuppressive regimens including autologous hematopoietic stem cell transplantation (AHSCT). Objective: The main objective of determining long-term insulin independence as well as changes in glycated hemoglobin (HbA1c). Secondary outcomes were procedure morbidity and the need for hospital management. Design: We enrolled patients with type 1 diabetes between 2012 and 2014. Median follow-up was 34 months (range, 25-56 mo). Setting: Ambulatory care. Interventions: We decided to carry out an AHSCT protocol using a less toxic and affordable simplified method based on fludarabine in an outpatient setting. Patients: Patients were of both sexes, age 8-25 years, with positive levels of anti-GAD antibodies, a C-peptide level >1.0 ng/mL, and >3 months since diagnosis. Main Outcome Measure(s): Insulin independence. Results: Sixteen patients were included. Overall response was 81% with seven patients achieving insulin independence (44%); six were partial responders (37%) whereas three were nonresponders (19%). The HbA1c level showed a mean decrease of -2.3% at 6 months in the Insulin Independence group. Median age was 12 years old (range, 8-17 years old). A mean of 11.5 × 106 CD34+ cells (SD ± 8.2) was obtained. Related mortality at 100 days was 0% as well as during follow-up. Outpatient setting was 100%. Conclusions: Simplified AHSCT in an outpatient setting is a feasible, safe and potentially therapeutic intervention for early-onset type 1 diabetes.